New book, Cognitive Enhancement, 1st Edition (Elsevier)

"This is an important and timely addition to the multidisciplinary field that has arisen to address the problems of cognitive decline and the competition for limited resources. Score: 98 - 5 Stars"

This new book contains a vast amount of information regarding traditional and modern strategies aimed at enhancing cognitive function, both in animals and humans. The editors made an effort to make this book accessible to the general public, although some of the chapters may be more scientifically orientated than others. Nevertheless, the general goal of this book is to bring together the bulk of information available in this field, in the hope that this will eventually help scientists to develop new, more efficient approaches to treat cognitive impairment.

What is Cognitive enhancement?

“Cognitive enhancement” is commonly associated with drug use or the use of devices to improve cognition. In this book we present an up-to-date overview of drugs, environmental conditions, and genetic factors related to cognitive enhancement in health and disease, gathering multidisciplinary knowledge and tools that will enable a further understanding of the topic. The chapters of the book have been written by top neuroscientists and they look in depth at a number of the traditional and cutting-edge technologies that are currently studied and employed in experimental animals and sometimes, in humans.

One of the most common approaches to develop new cognitive enhancers is to identify the pathways involved in learning and memory, and to test activators specific to these pathways. Having understood the signaling pathways that globally modulate learning and memory, it is essential to uncover the specific molecular and synaptic events mediating cognitive function. Accordingly, sophisticated molecular and electrophysiological tools based on the idea that facilitating synaptic plasticity may eventually lead to better cognitive function, a result that can be achieved by manipulating the activity of neurotransmitter receptors.

How can environmental and epigenetic factors improve cognition?

Control over the environment may represent a physiological approach to cognitive enhancement, focusing on how the incredible plasticity of the brain is used to evolve behaviors that accommodate the inherent uncertainty and probabilistic nature of the environment. We discuss how this plasticity requires a constant interaction between the genome and the environment, with epigenetic mechanisms.

What can we learn from smart transgenic mice?

We describes how cognitive functions are enhanced in some transgenic mice. Understanding the mechanisms of memory enhancement in these ‘smart mice’ is an important tool to elucidate the basic mechanisms underlying learning and memory, as well as to develop treatments for cognitive disorders.

Optogenetics is an innovative method that permits real-time control of genetically-defined neuronal populations using light-sensitive proteins. The incorporation of optogenetic tools into the field of learning and memory can be used for memory generation and cognitive enhancement.

We describe how multipotent stem cells within the adult brain play a critical role in cognition and the strategies to favor neural stem cell populations within key brain regions that are being developed to enhance cognition in rodents. Moreover, the brain’s capacity for plasticity and regeneration is reviewed, along with the potential role of endogenous neurogenesis and stem cell transplantation to augment this capacity.

What about Alzheimer’s disease and other neuropsychiatric disorders?

We describe the cognition-enhancing manipulations overcoming the cognitive deficits related to Alzheimer’s disease. Unfortunately, in most cases the strategies that have proven successful in rodents tend to fail in human beings. In some cases, the failure of the treatment can be easily traced, as when the treatment produced significant side-effects. However, in most cases there is no ready explanation for failure.

We summarize the approaches to enhance cognitive capabilities in humans using pharmaceuticals, nutrition, physical exercise, sleep, meditation, mnemonic strategies, computer training and brain stimulation. The mixed evidence for the efficacy of many pharmaceutical drugs currently used for cognitive enhancement is summarized, while a growing body of evidence for several non-pharmacological interventions indicates reliable cognition enhancing effects. In this respect, we provide valuable data on the use of non-invasive brain stimulation for cognitive enhancement, such astranscranial direct current stimulation (tDCS). The evidence of the safety, beneficial impacts and cost-benefit ratio of these techniques at the individual and societal level are discussed in detail, along with the mechanisms and physiological effects of tDCS, and its effects on human cognition.

Science fiction is here!

We describe possible scenarios that may currently sound unrealistic yet that serve to reflect on the danger of unregulated use of cognitive enhancers. This chapter explains why and how authorities should strictly control the prescription of cognitive enhancers, adapting state laws to these new technologies.

News

Neurons communicate with one another by synaptic connections, where information is exchanged from one neuron to its neighbor. These connections are not static, but are continuously modulated in response to the ongoing activity (or experience) of the neuron. This process, known as synaptic plasticity, is a fundamental mechanism for learning and memory in humans as in all animals. In fact, we now know that alterations in synaptic plasticity are responsible for memory impairment in cognitive disorders such as Alzheimer’s disease. Nevertheless, the mechanisms by which these alterations take place are still starting to be uncovered.

This new research work, published in Nature Neuroscience reports that in Alzheimer’s disease, synaptic plasticity is altered by a protein originally described as a tumor suppressor: PTEN. In 2010, the research group of Dr. Esteban discovered that PTEN is recruited to synapses during normal (physiological) synaptic plasticity. This new investigation by Drs. Knafo, Venero and Esteban, now indicates that this mechanism runs uncontrolled during Alzheimer’s disease. One of the pathological agents of the disease, the beta-amyloid, drives PTEN into synapses excessively, unbalancing the mechanisms for synaptic plasticity and impairing memory formation.

An important aspect of this study is that it also describes how PTEN is recruited to synapses in response to beta-amyloid, and proposes a strategy to prevent it. Using a mouse model of Alzheimer’s disease, the investigators developed a molecular tool to shield synapses from the recruitment of PTEN. With this tool, neurons are rendered resistant to beta-amyloid, and Alzheimer’s mice preserve their memory.

Although this is basic research using animal models, these studies contribute to dissect the mechanisms that control our cognitive function, and orient us towards potential therapeutic avenues for mental diseases where these mechanisms are deficient.

From the web: "A recent study in PLoS Biologyshould give hope to the forgetful. A collaborative research group in Europe, spanning Spain, Switzerland and Denmark, developed a small protein called FGL that enhances memory formation and learning in rats, and now they have some explanation as to why. The study’s authors, led by Shira Knafo, César Venero and José Esteban, attribute the improvement from FGL to better connections—and ability to strengthen those connections—between neurons. This knowledge may eventually improve treatment of some disorders, as the authors explain that these “mechanisms are thought to be responsible for multiple cognitive deficits, such as autism and Alzheimer’s disease”

How it might work

In their most recent article, the authors suggest that FGL improves the brain's ability to modify the connections between neurons, the cells that are the building blocks of the brain. When examining neurons that had been treated with FGL, Knafo, Venero and Esteban found that they had higher levels of a receptor, AMPA, critical for modifying neuronal connections.

As the authors write, "The human brain contains trillions of neuronal connections, called synapses, whose pattern of activity controls all our cognitive functions. These synaptic connections are dynamic and constantly changing in their strength and properties, and this process of synaptic plasticity is essential for learning and memory. In this study, we show that synapses can be made more plastic using a small protein."

Many neuroscientists consider understanding plasticity the Holy Grail for learning and memory; once we understand plasticity, we will understand how the brain learns.